Reactivity Patterns of (Protonated) Compound II and Compound I of Cytochrome P450: Which is the Better Oxidant?

Xiao Xi Li, Verònica Postils, Wei Sun, Abayomi S. Faponle, Miquel Solà, Yong Wang, Wonwoo Nam, Sam P. de Visser

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


The cytochromes P450 are versatile enzymes in human physiology that perform substrate hydroxylation reactions extremely efficiently. In this work, we present results of a computational study on the reactivity patterns of Compound I, Compound II, and protonated Compound II with model substrates, and we address the question of which of these compounds is the most effective oxidant? All calculations, regardless of the substrate, implicated that Compound I is the superior oxidant of the three. However, Compound II and protonated Compound II were found to react with free energies of activation that are only a few kcal mol−1 higher in energy than those obtained with Compound I. Therefore, Compound II and protonated Compound II should be able to react with aliphatic groups with moderate C−H bond strengths. We have analysed all results in detail and have given electronic, thermochemical, valence bond, and molecular orbital rationalizations on the reactivity differences and explained experimental product distributions. Overall, the findings implied that alternative oxidants could operate alongside Compound I in complex reaction mechanisms of enzymatic and synthetic iron porphyrinoid complexes.

Original languageEnglish
Pages (from-to)6406-6418
Number of pages13
JournalChemistry - A European Journal
Issue number26
StatePublished - 5 May 2017

Bibliographical note

Publisher Copyright:
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim


  • cytochrome P450
  • density functional calculations
  • electronic structure
  • hydroxylation
  • oxidation


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